Direct actions of cocaine on cardiac cellular electrical activity.

Abstract

The hypothesis that cocaine has Class I-type antiarrhythmic drug effects was tested in tissues isolated from rabbit heart with standard microelectrode methods. Propranolol (1 microM) was used to block beta-adrenergic effects. The actions of cocaine on cellular electrophysiology were concentration- and time-dependent and were reversible. In paced right atrial (RA) and right ventricular papillary (RVP) tissues, cocaine produced a profound prolongation of the effective refractory period (ERP) assessed by either premature stimulation or minimum pacing interval. ERP was increased up to eightfold in RA tissue and doubled in RVP tissue by 60 microM cocaine. This concentration of cocaine depressed action potential phase 0 depolarization 80% in RA tissue and 53% in RVP tissue but had no effect on resting membrane potentials. Automaticity was moderately depressed in sinus node (34% decrease in rate) but not in tricuspid valve cells. Phase 0 depolarization was not altered in these spontaneously active slow-response cells. Repolarization was depressed in RA, tricuspid valve, and sinus node cells leading to a twofold increase in action potential duration during exposure to cocaine. Evidence from the effects on cellular action potentials suggests that cocaine affects both fast Na+ channels and repolarizing K+ but not Ca2+ channels. We conclude that cocaine has Class I-type activity and the effects on ERP are extreme.

The effects of acute and chronic cocaine use on the heart.

“…On the ECG, this is manifested by a prolongation of the PR, QRS, and QT intervals35; cocaine also prolongs the refractoriness of atrial and ventricular muscle. 36 In this sense, the drug's electrophysiological properties are similar to other type I antiarrhythmic agents such as procainamide and quinidine. This direct local anesthetic or membrane-stabilizing property may be responsible for a negative inotropic effect of cocaine.…”

Sudden Cardiac Death With Apparently Normal Heart

“…The drug has class I-type activity, with significant effects on myocardial refractoriness. 40 In addition, cocaine can have a proarrhythmic effect similar to that induced by quinidine as the result of triggered activity from early afterdepolarizations associated with a prolonged QT interval. Thus, cocaine ingestion could induce ventricular arrhythmia independent of its effects on coronary arteries 41 and in the absence of toxic levels.…”

Early afterdepolarizations and triggered activity induced by cocaine. A possible mechanism of cocaine arrhythmogenesis.

“…Such conduction disturbances could contribute to the generation of reentrant arrhythmias, and previous investigators have emphasized this concept of cocaine arrhythmogenesis"~- 15; however, it has also been shown that cocaine prolongs repolarization. 15 In this respect, the effects of cocaine are similar to those of class IA antiarrhythmic drugs, that is, Na+ channel block and prolongation of repolarization. Class IA antiarrhythmic drugs, especially quinidine, have been shown to induce triggered activity arising from early afterdepolarizations (EADs), '8 19 which have been proposed as a potential mechanism of arrhythmias in patients with acquired long QT syndrome.…”

“…However, it has also been proposed that cocaine-related deaths of cardiac origin may occur in the absence of myocardial infarction, presumably because of direct adverse effects on cardiac electrophysiology. [11][12][13][14][15] Cocaine is a local anesthetic, and its blockade of Na+ channels1617 may produce conduction disturbances in the heart. Such conduction disturbances could contribute to the generation of reentrant arrhythmias, and previous investigators have emphasized this concept of cocaine arrhythmogenesis"~- 15; however, it has also been shown that cocaine prolongs repolarization.…”